Abstract Background Spatial navigation relies on egocentric and allocentric frames of reference, with the latter critically impaired in Alzheimer disease (AD) due to hippocampal involvement. Recent evidence suggests that egocentric representations may coexist within medial temporal lobe regions; however, their relative impairment in the early stages of AD remains unclear. Virtual reality offers a promising approach to bridge this gap by assessing spatial navigation abilities and providing sensitive digital biomarkers for AD. Objective This study investigates spatial memory performance in individuals with amnestic mild cognitive impairment (aMCI) using a virtual reality object-location memory task that manipulated available cues during recall. An environmental boundary probed hippocampal-dependent allocentric processing, while a discrete landmark probed striatal-dependent egocentric strategies. Methods Eighty participants (40 individuals with aMCI and 40 healthy controls HC) encoded object locations in a virtual arena and recalled them using either landmark or boundary cues. Results Regardless of the spatial frame of reference, patients with aMCI demonstrated significantly poorer overall spatial memory than the HC group. Surprisingly, virtual egocentric error emerged as a predictor of aMCI diagnosis. No differences were observed in frame-switching, object-location binding, or across recall trials. Analysis of virtual encoding paths revealed that patients with aMCI exhibited centrifugal navigation away from the discrete landmark and toward the boundary of the arena. During recall, patients with aMCI demonstrated less effective usage of boundary and landmark cues than HC, as revealed by the distribution of response coordinates. Conclusions These findings indicate that, in addition to well-documented allocentric deficits, egocentric spatial memory impairments provide a complementary and potentially sensitive marker within the AD continuum. This dual impairment of spatial cognition systems may enhance our understanding of navigational difficulties in aMCI and offers insight into the nature of spatial representations in aging.
Tuena et al. (Wed,) studied this question.